Tricarbocyanine infrared absorbing dyes



Wi W Pa Q 2,895,955 H'IRICARBOCYANINEDISIFESFRARED ABSORBING Donald W.Heseltine and Leslie SiBrooker, Rochester,

N.Y., assignors to Eastman Kodak Company, Rochester, N.Y., acorporationvof New Jersey N Drawing. Application June 5, 1957 Serial No.663,578

4 Claims. (Cl. 260-2405) This invention relates to tricarbocyanine dyescontaining a benzEelindole nucleus which have usefiul infrared absorbingproperties.

The tricarbocyanine dyes of our invention can advantageously berepresented by the following general formula:

wherein R- represents an "alcohol radical, i.e., an alkyl group(substituted or unsubstituted), containing not more than4 carbon.atoms,'such as methyl, ethyl, n-butyl, sulfoethyl, 4-sulfobutyl,3-sulfobutyl, etc., and X represents an acid radical, such. as chloride,bromide, iodide,

p-toluenesulfonate, etc. r

Thedy es of Formula I above can be prepared by condensing a cyclammoniumquaternary salt selected from those represented by the following generalformula: (I'I).',YY a

wherein Rand X each have the values given above with"glutaconic-aldehyde dianilide hydrochloride in the'presence of acarboxylicanhydridefsuch as acetic, propionic,

butyric, etc., anhydrides. This general method of prep aration oftricarbocyanine dyes is described in Keyes U.S.

Patent 2,251,286, dated'Aug'ust S, 1951.

As shown in Patent 2,251,286, the first step in the con densationinvolves the formation of an acylanilido den'vative. In some'instances,improved yields can be obtained by'isolatin'g this acylanilido compoundand reactingit with a'second molecule of the compound of Formula 7 x V Ip 'Heat acce'lerates the condensations, and since the carw it 2,895,9551 Patented July 21, 1959 vcc:

boxylic anhydrides generally employed as condensing :1 7 agents areliquids, it is convenient simply to reflux the .or salts of weak acids,such as sodium acetate, etc., can

be used.

The intermediates of Formula II above can conveniently be prepared byheating the compound of the following formula:

with a compound of the following general formula:

wherein n represents a positive integer of from. 3 to 4,

to provide those compounds wherein R of Formula II "represents asulfoalkyl group. I The reaction of the com-1 pound ofFormula'IIIwith'tho'sje of Formula IV provides cyclammonium quaternary saltscontaining no combined; acid radical. These products are generallyknown'as" vbetaines. --The methylene group of the compounds of;

Formula IV can carry-simple substituentgsuch ets-methyl groups, ethylgroups, etc. I 1 The following examples will serve to illustrate morefully the manner whereby we practice our invention.

indotricarbocyanine chloride $113 C l lg xcl1,1,2-trimethy1benzielindole (10.45 g., 2 mols.) and methylp-toluenesulfonate (1Q.2 g 2 mols. plus 20%) Were'mixed and heated onthe steam bath for thirty minutes and were then allowed to stand at roomtemper-i ature overnight. Glutajconicaldehyde' dianilide hydro chloride(7 .2 g'.,'-1mol.) and timely powdered fused sodium acetate were-thenadded to the quaternary salt. Boiling acetic anhydride in.) was thenadded and the re? action mixture heated under reflux f or twenty;minuteThe reaction mixture was then poured with stirring into one liter ofcold water containing sodium iodide (10 g.).

Example 4.Anhydro-2,3,3-trimethyl-1-(4 sulfobutyl)-4,5,4,5'-dibenzoindotricarbocyanine iodide disodium salt I (8 92 (g ahAnhydro-2-(6-acetanilido-1,3,5 hexatrienyl)-3,3dimethyl-l-(4-sulfobutyl)4,5-benzopseudoindolium hydroxide (5.42 g., 1mol.) and anhydro-2,3,3-trimethyl-1-(4-sulfobntyl)-4,--benzopseudoindolium hydroxide (3.45 g.,

. 1 mol.) were dissolved in ethyl alcohol (30 ml.) and triethylamine(1.4 ml., 1 mol.) was added. The mixture was then heated under reflux.for. fifteen minutes. After cooling, the crude dye was thrown out ofsolution by the addition with stirring of ether (100 ml.). The ether wasdecanted and the residue dissolved in methyl alcohol (100 1111.),filtered and treated with sodium iodide (5 g.) dissolved in methylalcohol (25 ml.). The crude dye was collected on a filter, washed withacetone and dried. The crude dye was purified by dissolving in methanoland precipitating by the addition of alcoholic sodium iodide. The crudeproduct was then twice refluxed with two liter portions of acetone andfiltered from the hot suspension. The yield of purified dye was 7.5 g.(83%) M.P. 243-5 C. dec. 1

Example 3.--Anhydro-2-(6-acetanilid0 1,3,5hexatrienyl)-3,3-dimethyl-1-(4 sulfobutyl)-4,5 benzopseudoindoliumhydroxide Anhydro-2,3,3- trimethyl-1-(4sulfobutyl)-4,5-benwpseudoindolium hydroxide (17.3 g., 1 mol.) andglutaconicaldchyde dianilide hydrochloride (15.6 g., 1 mol. plus 10%)were added with stirring to boiling acetic anhydride (100 ml.). Thesource of heat was removed and the stirring continued for thirtyminutes. Afterchilling, the crystalline product was collected on afilter, washed with acetone and, dried. The yield of product was 24.1g..(90%) M.P. 168-70 C. dec.

4,5-benzopseudaindolium hydroxide LLZ-trimethylbenzielindole (20.9 g., 1mol.) and 1,4-butanesultone (13.6 g., 1 mol.) were mixed and heated onan oil bath for two hours at 130 C. The solid-cake was then ground underacetone, collected on a filter, washed with acetone and dried. The yieldwas 26.0 g.,.

A sample recrystallized from methanol and acetone had M.P. 266-7 C. dec.

The compounds of our invention are useful in diagnosing certaincirculatory disorders, particularly congenital heart defects. Theutility of our compounds is based upon their property ofabsorbingstrongly in the infrared at about 800 m while having very :little or noabsorption in the visible part of the spectrum. The dyes of ourinvention are readily dissolved in water andthe aqueous solutionsobtained can be injectedinto the bloodstream 1 and the passage of thedye through the circulatory system measured. The technique of observingthe passage of the dye throughthe blood stream has been previouslydescribed in detail in the prior art. See, for example, Americanlournalof Physiology, vol. 187, No. 3, December 1956. The quantity of dyeinjected into the blood stream is, of course, dependent upon thebodyweight of i the subject. In general, about 0.1 nag/kilogram of bodyweight is sufficient.

The infrared absorbing dyes of our invention also have usefulphotographic properties, although they have little trum. During theprocessing and handling of silver halide emulsions intended for infraredphotography, the dyes of our invention can be employed in conjunctionwith a Wratten filter which absorbs blue light (e.g., a Wratten No. 12filter) to provide a convenient safe-light. To prepare a suitableWratten type filter using our new dyes, it

is convenient to simply dissolve the dyes in distilled water, and addsufiicient solution to an ordinary gelatin suspension, to provide thedegree of absorption required, and then coat this dyed gelatin solutionon a conventional support, such as glass, cellulose ester film, etc.,and dry the coating.

The dyes of our invention can also be employed in color photographyinvolvingthe use of multilayer, differentially sensitized emulsionswhere it is desired to re- 1 move infrared radiation. For this purpose,the dyers of our invention can be incorporated in the silver halideemulsion layers of the multilayer element, or they can be employed in aseparate layer, such as; an overcoating. layer. The dyes of ourinventionare particularly useful for this purpose, since'they do not have anysubstantial effect on the color balance of the multilayer element.

The term sulfo as used in the foregoing specification and in thefollowing claims includes the --SO H group as well as the salt forms ofthis group. Typical salts of this group include the alkali metal salts(e.g., sodium, potassium, etc.), as well as ammonium and organicammonium salts (e.g., triethylammonium, triethanolammonium, pyridinium,etc.). The compounds of Formula I above containing a sulfo substituenton the alkyl group have been found to be of outstanding importance andprovide improved results over those obtainable with the simple,unsubstituted alkyl compounds. This is particularly true in using thesecompounds in diagnosing heart conditions, since certain dyes might havea tendency to precipitate from the blood stream and be of little valuein determining the condition of the circulatory system. The dyes of ourinvention containing a sulfo group have been found to be particularlyfree of precipitation effects. When used in medical diagnosis, ourcompounds appear to have no adverse effects on the patient.

What we claim as our invention and desire to secure by Letters Patent ofthe United States is:

1. A water-soluble tricarbocyanine dye selected from those representedby the following general formula:

(gnu),

wherein R represents a sulfoalkyl group containing from 1 to 4 carbonatoms and X represents a non-toxic acid anion.

3. The tricarb'ocyanine dye represented by the following formula:

4. The tricarbocyanine dye represented by the following formula:

OTHER REFERENCES Brooker: Journal of the American Chemical Society, vol.63, pp. 3192-3203 (1941).

1. WATER-SOLUBLE TRICARBOCYANINE DYE SELECTED FROM THOSE REPRESENTED BYTHE FOLLOWING GENERAL FORMULA: